This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this research is to help us to determine the underlying mechanisms involved in the regulation of skeletal muscle loss and regrowth in older adults after complete knee replacement surgery (also known as total knee arthroplasty or TKA). We will determine if the ability of muscle growth is influenced by physical therapy followed by ingesting a nutrient solution containing muscle protein building blocks (essential amino acids). We will determine if the ability of muscle growth is influenced by physical therapy. To measure the potential negative affects of total knee replacement surgery we will use stable amino acid isotopes to the subjects before and after their surgery. We will take muscle biopsies of the thigh muscle to determine the rate at which each subject is producing muscle protein and measure the changes in signals produced by muscle are responsible for muscle growth. To measure the affects of physical therapy with or without a growth promoting nutrient solution of essential amino acids we will study each subject 4 days after their surgery (they will have less pain and more mobility on day 4) before (while lying in bed) and after a session of physical therapy + placebo or physical therapy + growth promoting nutrient solution. These studies will first give us an understanding of the effects of total knee replacement surgery on muscle metabolism and shed light on traditional methods used to regain strength following this surgery (i.e., physical therapy).